The major component in schistosome eggs responsible for conditioning dendritic cells for Th2 polarization is a T2 ribonuclease (omega-1)

Steinfelder, Svenja; Andersen, John F.; Cannons, Jennifer L.; Feng, Carl G.; Joshi, Manju B.; Dwyer, Dennis M.; Caspar, Patricia; Schwartzberg, Pamela L.; Sher, Alan; Janković, Dragana

doi:10.1084/jem.20082462

Cited by 265 publications

(290 citation statements)

References 35 publications

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“…This finding presents the possibility that the potential Syk-coupled receptor, which is activated by SEA, is a lectin receptor. In association, C-type lectin receptors have been shown to partially mediate the internalization of these antigens, which may highlight the necessity of sugar components in SEA (6, 28,29). This study has deciphered that SEA specifically signals through the C-type lectin receptor Dectin-2, but not Dectin-1 or other receptors such as CD206, CD36, and DAP12.…”

Section: Discussionmentioning

confidence: 93%

“…SEA is a complex mixture of proteins, glycoproteins, and glycolipids (28,29), and our studies show that SEA-mediated IL-1β production was abolished upon heat inactivation and proteinase K digestion, demonstrating that the responsible component might be a protein. Interestingly, the inactivation of SEA did not alter the TNF-α suppression, suggesting that different components within SEA can act in tandem and thus balance ongoing immune responses.…”

Section: Discussionmentioning

confidence: 95%

“…Therefore, we consider that this mechanism is not used by SEA. Several studies have postulated that the inflammasome is triggered by different upstream events such as potassium (K + ) efflux or ROS production (17,19,(28)(29)(30). To elucidate the role of these intermediary signals, we treated BMDCs with potassium chloride (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Schistosomamansonitriggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses

Ritter

Groß

Kays

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

216

204

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The propensity of helminths, such as schistosomes, to immunomodulate the host's immune system is an essential aspect of their survival. Previous research has demonstrated how soluble schistosomal egg antigens (SEA) dampen TLR-signaling during innate immune responses. We show here that the suppressive effect by SEA on TLR signaling is simultaneously coupled to the activation of the Nlrp3 (NLR family, pyrin domain containing 3) inflammasome and thus IL-1β production. Therefore, the responsible protein component of SEA contains the second signal that is required to trigger proteolytic pro-IL-1β processing. Moreover, the SEA component binds to the Dectin-2/FcRγ (Fc receptor γ chain) complex and activates the Syk kinase signaling pathway to induce reactive oxygen species and potassium efflux. As IL-1β has been shown to be an essential orchestrator against several pathogens we studied the in vivo consequences of Schistosoma mansoni infection in mice deficient in the central inflammasome adapter ASC and Nlrp3 molecule. These mice failed to induce local IL-1β levels in the liver and showed decreased immunopathology. Interestingly, antigen-specific Th1, Th2, and Th17 responses were down-regulated. Overall, these data imply that component(s) within SEA induce IL-1β production and unravel a crucial role of Nlrp3 during S. mansoni infection.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Schistosomamansonitriggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses

Ritter

Groß

Kays

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

216

204

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“…Helminth parasites are known to release a wide variety of enzymatically active products that are With regard to the effects of such molecules on DC, omega-1, a glycosylated RNase secreted by schistosome eggs and present in SEA, was recently found to drive Th2 responses via functional modulation of DC [37,45]. Interestingly, omega-1 could modulate DC function in vitro with characteristics similar to those of SEA, while depletion of omega-1 from SEA abrogated to a large extent its potential to modulate DC function as determined by its capacity to suppress DC LPS-induced IL-12 secretion, expression of maturation markers, and its ability to drive Th2 polarization.…”

Section: Modulation Through Prr-signaling Independent Mechanismsmentioning

confidence: 99%

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

et al. 2010

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The classical reaction of the host to helminth infections is the induction of Th2 immune responses with a regulatory component. DC, as central players in the induction and maintenance of immune responses, play a prominent role in both these processes, and in recent years considerable progress has been made in elucidating the mechanisms behind the interplay between DC and helminths. It is becoming increasingly clear that helminths modulate DC function not only via direct interactions but also indirectly via host-derived cues. Furthermore, while studies have until recently focused on receptor signalingmediated DC modulation by helminths, evidence is emerging that DC may also respond to helminth infections by sensing stress signals or tissue damage inflicted by the worms or their products. Here, we will discuss these new insights and will link them to the origin and importance of Th2 and regulatory immune responses with respect to the survival of both parasite and host.Key words: DC . Helminth . Th cell polarization . Tissue damage IntroductionThe classical reaction of the host to helminth infections is the induction of Th2 responses. The induction of Th2 immunity has been shown to be important for resistance to helminth infections in various model systems; however, despite induction of a Th2 response, total clearance of the parasites rarely occurs in man (reviewed in [1,2]). This implies that helminths have evolved strategies, such as evasion or suppression of the host immune response that prevent their expulsion and permit their long-term survival. The immune modulatory effects are thought to arise from the helminth's capacity to exploit the host's own system of immune regulation, which is normally crucial for the maintenance of immune homeostasis and self tolerance. In this respect, the induction of Treg has been shown to be one of the most common mechanisms that restrains immune responses against the parasite while also preventing excessive inflammation and tissue damage inflicted by the worms (reviewed in [2,3]). Therefore, it is not surprising that among the variety of mechanisms developed by helminths to influence host immune responses, modulation of DC as pivotal players in the initiation and polarization of adaptive immune responses, including Treg modulation, may have a particularly important role (reviewed in [2,4,5] ) carbohydrate epitope found in schistosoma soluble egg antigens (SEA), has been implicated in TLR4-dependent priming of Th2 responses via DC [9]. However, SEA is also known to be capable of modulating DC for Th2 priming in the absence of TLR signaling [10]. Furthermore, phosphatidylserine (PS) lipids derived from schistosomes and ascaris worms, which carry TLR2-activating molecules, have been shown to promote Th2 responses via DC, but this is not TLR2 dependent [11], whereas monoacetylated PS lipids from schistosomes were found to specifically instruct DC to preferentially induce IL-10-producing Treg in a TLR2-dependent fashion [12]. Although TLR2 does not seem to be essential for Th2 polar...

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“…43,44 In addition, soluble egg antigens from S. mansoni is enriched in omega-1, which modulates DCs and induces the expression of Foxp3 in T cells in vitro. 45,46 Although the restrained immune response in malaria and schistosomiasis is a problem, the impairment in DC function may become useful for the control of chronic inflammatory conditions. Likewise, DCs exposed to soluble egg antigens and omega-1 acquire modulatory properties and induces Treg cells in CD4 + T cells from non-obese diabetic (NOD) mice, reducing the incidence of spontaneous diabetes.…”

Section: Discussionmentioning

confidence: 99%

Dendritic cells treated with crude Plasmodium berghei extracts acquire immune‐modulatory properties and suppress the development of autoimmune neuroinflammation

et al. 2014

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SummaryDendritic cells (DCs) are professional antigen-presenting cells specifically targeted during Plasmodium infection. Upon infection, DCs show impaired antigen presentation and T-cell activation abilities. In this study, we aimed to evaluate whether cellular extracts obtained from Plasmodium berghei-infected erythrocytes (PbX) modulate DCs phenotypically and functionally and the potential therapeutic usage of PbX-modulated DCs in the control of experimental autoimmune encephalomyelitis (EAE, the mouse model for human multiple sclerosis). We found that PbX-treated DCs have impaired maturation and stimulated the generation of regulatory T cells when cultured with naive T lymphocytes in vitro. When adoptively transferred to C57BL/6 mice the EAE severity was reduced. Disease amelioration correlated with a diminished infiltration of cytokine-producing T cells in the central nervous system as well as the suppression of encephalitogenic T cells. Our study shows that extracts obtained from P. berghei-infected erythrocytes modulate DCs towards an immunosuppressive phenotype. In addition, the adoptive transfer of PbX-modulated DCs was able to ameliorate EAE development through the suppression of specific cellular immune responses towards neuro-antigens. To our knowledge, this is the first study to present evidence that DCs treated with P. berghei extracts are able to control autoimmune neuroinflammation.

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The major component in schistosome eggs responsible for conditioning dendritic cells for Th2 polarization is a T2 ribonuclease (omega-1)

Cited by 265 publications

References 35 publications

Schistosomamansonitriggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses

Schistosomamansonitriggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

Dendritic cells treated with crude Plasmodium berghei extracts acquire immune‐modulatory properties and suppress the development of autoimmune neuroinflammation

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